PROJECT SUMMARY/ABSTRACT Rates of mild cognitive impairment (MCI) and dementia are two to three times higher among African Americans (AAs) than among White older adults. Observational and clinical trial data, most recently from the Systolic Blood Pressure Intervention Trial: Memory and Cognition in Decreased Hypertension (SPRINT-MIND), support that blood pressure is the most important modifiable vascular risk factor for MCI and dementia. However, the short duration of follow-up in SPRINT-MIND coupled with the failure to detect a statistically significant benefit of a lower blood pressure goal for incident dementia means that longer-term observational data will be necessary to fully address the implications of the clinical trial results. These questions are particularly salient for AAs, who have earlier onset of high blood pressure and are at higher risk of dementia, in particular cerebrovascular pathology. Even after considering race/ethnic differences in blood pressure level, the mechanisms underlying racial disparities in risk for dementia are not well understood. Additionally, despite facing a high burden of high blood pressure, some individuals are resilient, achieving better-than-expected outcomes. The specific factors that contribute to brain-health resilience are not well established. We propose to address these research gaps in an ancillary study to the 2020-2022 4th examination of ~2,700 participants in the Jackson Heart Study (JHS), an ongoing cohort study of well-characterized AAs. The JHS Exam 4 will include brain magnetic resonance imaging (MRI) data to ascertain cerebrovascular disease and neurodegeneration. We propose to add measures of cognition and function sufficient for classification of MCI and dementia, and innovative plasma biomarkers of amyloid (Ab42, Ab40), tau, and neurodegeneration (neurofilament light). The primary aims are as follows: Aim 1. Estimate the long-term associations of exposure to high 20-year time-weighted average blood pressure and blood pressure load on (1) cognitive performance; (2) prevalence of MCI and dementia; (3) markers of cerebrovascular disease and neurodegeneration quantified from MRI; and (4) plasma amyloid, tau and neurodegeneration. Aim 2. Examine whether sex, educational quality (i.e. reading level measured with the WRAT), and APOE-e4 and ABCA7 genotype, modify the associations of long-term exposure to high blood pressure and blood pressure load with cognitive outcomes. This study is responsive to PAR-19-070 and NOT- AG-18-047 (Health Disparities and Alzheimer?s Disease) by adding cognitive assessments to a landmark cohort study of cardiovascular disease in AAs; leveraging existing and new data to understand risk and resilience factors for cognitive impairment; and drawing on the JHS cohort to understand vascular mechanisms underlying cognitive impairment in a minority population. This study is also proposed in the context of the updated National Institute on Aging/Alzheimer?s Association research framework in which the constructs of amyloid, tau, and neurodegeneration are featured prominently. Lastly, results from this study will inform future research and have implications for policies intended to improve brain aging in minority populations.